Aspirin use benefits reduced by statins in those without atherosclerotic disease

1st March 2023

The benefits of aspirin use in myocardial infarction are offset by statin use in patients without atherosclerotic cardiovascular disease

Aspirin use for the prevention of myocardial infarction (MI) appears to be reduced by concomitant statin use in patients without atherosclerotic cardiovascular disease (ASCVD) without affecting the risk of a major bleed according to a meta-analysis by US researchers.

In 2019, US guidance suggested that aspirin should be used infrequently in the routine primary prevention of ASCVD because of lack of net benefit. More recently, the US Preventative Services Task Force has endorsed these earlier recommendations for primary prevention in adults aged between 40 and 59 with a 10% or higher, 10-year risk of CVD. While historically, aspirin was considered to reduce the risk of an MI, in the context of use with other strategies such as statins, one analysis concluded that the effect of aspirin on myocardial infarction risk was significantly attenuated, whereas its major bleeding and haemorrhagic stroke complications were retained.

For the current meta-analysis, researchers wanted to examine the impact on aspirin use with and without statins, specifically in those without ASCVD but at different levels of risk. The team included a range of risk levels from very low (< 5%) through to very high (> 30%). They included trials where patients were prescribed aspirin and followed for at least 12 months and the team determined the absolute risks for cardiovascular outcomes, major bleeding and mortality over 5 years.

Aspirin use with and without statins

In a total of 16 trials with 171,215 patients with a median age of 64 years (46% women), the use of aspirin alone was associated with a 15% lower risk of a myocardial infarction (risk ratio, RR = 0.85, 95% CI 0.77 – 0.95) although the drug did not reduce mortality. However, the drug lead to a higher risk of major bleeding (RR = 1.48, 95% CI 1.32 – 1.66, p < 0.001).

When considering the absolute benefits, the researched calculated that aspirin monotherapy in patients with a very low ASCVD risk, was likely to lead to 3 fewer myocardial infarctions (MIs) per 10,000 patients but 21 more major bleeds. In contrast, when taken in conjunction with a statin, there would be only 1 less MI but 20 more major bleeds. At the other extreme of ASCVD risk (i.e., > 30%), monotherapy might lead to 49 fewer MIs (but 98 major bleeds) but in combination with a statin, there would be 37 fewer MI’s but 94 major bleeds.

The authors concluded that among adults who did not have ASCVD, statin use with aspirin, appeared to attenuate to some extent aspirin’s clinical benefit but without influencing the bleeding risk, suggesting that the risk of a major bleed from taking aspirin exceeded its benefits across all levels of ASCVD risk.

Citation
Khan SU et al. Aspirin With or Without Statin in Individuals Without Atherosclerotic Cardiovascular Disease Across Risk Categories. JACC Adv 2023

Aspirin use in residual breast cancer disease improves distant metastases free survival 

28th October 2022

Aspirin use in breast cancer patients with residual disease after neoadjuvant chemotherapy led to improved distant metastases free survival

Aspirin use in women with breast cancer who were unable to achieve nodal clearance after neoadjuvant chemotherapy, significantly improved 5-year distant metastases free survival according to the findings of an analysis presented at the World Cancer Congress in Geneva, 2022 by researchers from University of Texas Southwestern, Dallas, US.

Breast cancer affects a huge number of women with data from the World Health Organisation suggesting that globally in 2020, there were 2.3 million diagnoses and 685 000 deaths. However, survival depends to a large extent on how far the disease has spread. For example, where localised, 5-year survival is 99% but if the disease has become more widespread, survival drops to 29%. Triple negative breast cancer is a particularly aggressive form of the disease such that if this form becomes metastatic, 5-year survival reduces to 12%. In a 2017 small study of 65 patients with triple negative breast cancer and stage II or III disease, researchers found that use of anti-platelet agents such as aspirin, led to significant improvements in 5-year disease-free survival and distant metastases rate. In addition, other work in patients with high-risk prostate cancer has also shown that aspirin use led to improved overall survival.

A pathological complete response (pCR) represents a state in which there is complete eradication of invasive carcinoma, for example, from breast and axillary lymph nodes as well as within blood or lymph vessels. This measure has been proposed as a surrogate endpoint for prediction of long-term clinical benefit, such as disease-free survival, event-free survival and overall survival. In fact, one analysis suggests that breast cancer patients who achieve pCR after neoadjuvant chemotherapy had a 64% lower risk of death compared to those who had residual disease at the time of surgery.  Furthermore, a higher residual cancer burden disease is significantly associated with worse event-free survival. Nevertheless, whether aspirin use in patients with residual disease confers any benefits is uncertain and was examined in the present study.

Researchers retrospectively identified patients without a pCR and with residual node disease after neoadjuvant chemotherapy and focused on the effect among those prescribed aspirin. The outcomes of interest were overall survival (OS), disease-free survival (DFS) and distant metastases-free survival (DMFS) using Kaplan Meier analysis and logistic regression.

Aspirin use and survival outcomes

A total of 637 patients, 48 of whom with a median age of 48 years were using aspirin, were followed-up 3.7 years.

Disease free survival was significantly higher among those using aspirin (Hazard ratio, HR = 0.54, 95% CI 0.32 – 0.92, p = 0.024) although DMFS was non-significant (HR = 0.63, 95% CI 0.38 – 1.05, p = 0.07). In contrast, in multivariate analysis among those with residual disease, aspirin use was significantly associated with an improvement in DMFS (HR = 0.52, 95% CI 0.29 – 0.94, p = 0.031).

The authors concluded that among breast cancer patients who have residual disease following neoadjuvant chemotherapy, aspirin use appeared to be associated with a significant improvement in 5-year disease and distant metastases survival. They added that future research should consider augmented aspirin use in high-risk breast cancer patients who do not achieve pCR.

Citation
Johns C et al. Aspirin Use is Associated with Improvement in Distant Metastases Outcome in Patients with Residual Disease after Neoadjuvant Chemotherapy Number 2009 World Cancer Congress, 2022

Aspirin use linked to increased risk of heart failure

29th November 2021

Aspirin use among patients both with and without cardiovascular disease is associated with an increased risk of incident heart failure

Aspirin use is associated with an more than a 20% increased risk of heart failure in those with and without cardiovascular disease according to the results of an analysis by researchers from the Research Unit Hypertension and Cardiovascular Epidemiology, University of Leuven, Belgium.

Heart failure (HF) is best described as a clinical syndrome and which is characterised by symptoms including breathlessness, ankle swelling and fatigue, due to structural and/or functional cardiac abnormality, leading to a reduced cardiac output and/or intra-cardiac pressures at rest or during stress. Furthermore, HF is associated with a associated with a hyper coagulable state and autopsy studies have found that acute coronary events are frequent in HF patients who die suddenly, highlighting the potential value of using anti-thrombotic therapy. Although low dose aspirin is no longer recommended for the primary prevention of cardiovascular disease, the role of anti-thrombotic therapy in heart failure is less clear with one study concluding that there was ‘no evidence that aspirin is effective or safe in patients with heart failure.’ In contrast, a 2014 study concluded that ‘low-dose aspirin therapy was associated with a significant reduction in mortality and morbidity risk’ in patients with heart failure.

With some uncertainty over the value of aspirin use in patients with HF, the Belgian researchers sought to gain a better understanding of the role and value of aspirin. They turned to the Heart ‘Omics’ in aGEing (HOMAGE) database, which contains patient-level data for over 30,000 individuals from 21 studies and developed models to examine the impact of aspirin using both a derivation and validation set. At baseline all participants were free of heart failure and at the time of entry into studies, aspirin use was recorded and patients dichotomised as either ‘users’ or ‘non-users’. Other data included in the subsequent analysis were demographics and relevant clinical information such as the presence of co-morbidities and any history of cardiovascular disease.

Findings

In the HOMAGE dataset, the study population included 30,827 individuals (19,257 in the derivation set) with a mean age of 66.8 years (33.9% women). Overall, 26.4% had a a history of coronary artery disease and the biggest co-morbidity was hypertension (85.8%).

After a median follow-up period of 5.3 years, 1330 patients experienced either fatal or non-fatal HF with an incident rate of 14.5% (95% CI 13.4 – 15.7%) in the aspirin use group versus 5.9% (95% CI 5.5 – 6.4%) in the ‘non-aspirin’ group. In the HOMAGE dataset, the fully adjusted hazard ratio for aspirin use in those with cardiovascular disease was 1.26 (95% CI 1.12 – 1.41, p < 0.001) and 1.23 (95% CI 1.06 – 1.41, p = 0.004) among those without cardiovascular disease.

Commenting on these findings, the authors concluded that aspirin use increased the risk of incident HF in patients with and without prior cardiovascular disease, adding that ‘our observations suggest that aspirin should be prescribed with caution in patients at risk of HF or having HF.’

Citation

Mujaj B et al. Aspirin use is associated with increased risk for incident heart failure: a patient‐level pooled analysis. ESC Heart Fail 2021